crossing96/oncoscreening huggingface dataset:
UBE2C is a marker of unfavorable prognosis in bladder cancer after radical cystectomy.	It has been suggested that ubiquitin-conjugating enzyme E2C (UBE2C, also known as UBCH10) represents a promising cancer biomarker. However, the clinicopathological or prognostic significance as well as the functions of UBE2C in bladder cancer are largely unknown. To investigate the significance of UBE2C expression in bladder cancer, immunohistochemical analysis was performed using a tissue microarray. UBE2C positivity was observed in 51 of 82 (62%) bladder urothelial carcinoma cases treated with radical cystectomy. In contrast, UBE2C was negative in all of the non-neoplastic urothelium examined. UBE2C positivity was significantly associated with higher tumor stage (p=0.0061) and presence of lymphovascular invasion (p=0.0045). In addition, UBE2C positivity was significantly associated with shorter cancer-specific survival after cystectomy (log rank p=0.0017; multivariate hazard ratio, 2.49; 95% confidence interval, 1.09-5.71). Small interfering RNA-mediated suppression of UBE2C in UM-UC-3 bladder cancer cells inhibited cell proliferation in vitro. Taken together, our results suggest that UBE2C is a novel prognostic biomarker as well as a potential therapeutic target in bladder cancer.	bladder
Macrophage migratory inhibitory factor promotes bladder cancer progression via increasing proliferation and angiogenesis.	Macrophage migratory inhibitory factor (MIF) is a proinflammatory cytokine shown to promote tumorigenesis. Using the N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) model of bladder cancer, we previously showed that MIF knockout mice display decreased angiogenesis and invasion compared with wild-type. This study examines the role of MIF in bladder cancer via use of oral inhibitors of MIF. In vitro, high-grade bladder cancer cells were treated with recombinant human MIF +/- (rhMIF+/-) inhibitor. Measurements included cell counts, proliferation by (3)H-thymidine incorporation (TdR), extracellular signal-regulated kinase (ERK) phosphorylation by western blot analysis, messenger RNA (mRNA) expression by quantitative PCR and protein secretion by enzyme-linked immunosorbent assay. Treatment with rhMIF increased ERK phosphorylation, cell counts, TdR and mRNA expression and protein secretion of vascular endothelial growth factor, which were blocked by specific inhibitors of ERK and MIF. In vivo, 3-month-old male C57Bl/6 mice were given BBN for 22 and 16 weeks in study 1 and study 2, respectively. Mice (n = 8-10 per group) were gavaged with vehicle or doses of MIF inhibitors daily from weeks 16-22 in both studies. Average bladder weights, reflecting tumor mass, tumor stage/burden, mitotic rate and proliferation indices, and microvessel densities were reduced in inhibitor groups versus controls. In summary, MIF promotes bladder cancer via increasing cell proliferation and angiogenesis and oral inhibitors of MIF may prove useful in treatment of this disease.	bladder
Development and characteristics of preclinical experimental models for the research of rare neuroendocrine bladder cancer.	PURPOSE: For rare cancers such as neuroendocrine bladder cancer treatment options are limited due partly to the lack of preclinical models. Techniques to amplify rare primary neuroendocrine bladder cancer cells could provide novel tools for the discovery of drug and diagnostic targets. We developed preclinical experimental models for neuroendocrine bladder cancer. MATERIALS AND METHODS: Fresh tumor tissue from 2 patients with neuroendocrine bladder cancer was used to establish in vitro and in vivo models. We analyzed additional archived tissues in the National Center of Tumor Diseases tissue bank from patients with neuroendocrine bladder cancer. Primary tumor samples were collected during radical cystectomy. PHA-665752 was used to inhibit MET in animal models and cell cultures. The expression of markers and drug targets in neuroendocrine bladder cancer was determined by flow cytometry. The growth of neuroendocrine bladder cancer in vitro was determined by counting live cells. Tumor growth in mice was assessed by measuring tumor volume. Groups were compared using the nonparametric Kruskal-Wallis test. RESULTS: Xenograft models and serum-free cultures of neuroendocrine bladder cancer cells allowed screening for cell surface markers and drug targets. We found expression of the HGF receptor MET in neuroendocrine bladder cancer cultures, xenograft models and primary patient sections. The growth of neuroendocrine bladder cancer spheroids in vitro depended critically on HGF. Treatment of neuroendocrine bladder cancer bearing mice with a MET inhibitor significantly decreased tumor growth compared to that in control treated mice. CONCLUSIONS: Neuroendocrine bladder cancer xenografts and serum-free cultures provided suitable models in which to identify diagnostic markers and therapeutic targets. Using the models, we noted HGF dependent growth of human neuroendocrine bladder cancer and identified MET as a new treatment target for neuroendocrine bladder cancer.	bladder
Human β-defensin 2 may inhibit internalisation of bacillus Calmette-Guérin (BCG) in bladder cancer cells.	OBJECTIVE: To investigate whether secretion of human β-defensin 2 (HBD-2) is induced by bacillus Calmette-Guérin (BCG) and to determine whether HBD-2 affects BCG internalisation in bladder cancer cells. MATERIALS AND METHODS: Reverse transcription-polymerase chain reaction analysis was used to determine whether HBD-2 mRNA increases after incubation with BCG. HBD-2 proteins in 5637 and T24 human bladder cancer cell lines were assayed by enzyme-linked immunosorbent assay. The internalisation rate was evaluated by double immunofluorescence assay and confocal microscopy to test the optimal dose of HBD-2 for BCG internalisation. We also investigated the difference in internalisation rates and cell viability between recombinant HBD-2 protein, anti-HBD-2 antibody, and HBD-2 plus anti-HBD-2 antibody pretreatments. RESULTS: BCG induced HBD-2 mRNA expression and HBD-2 production dose and time-dependently in bladder cancer cells and affected BCG internalisation. Pretreatment with recombinant HBD-2 protein lowered internalisation of BCG dose-dependently. Moreover, anti-HBD-2 antibody prevented the effect of HBD-2 on BCG internalisation in bladder cancer cells. The internalisation rate of BCG pretreated with anti-HBD-2 antibody was higher than that in the control in 5637 (P < 0.01) and T24 cells (P < 0.05). The BCG internalisation rate in cells pretreated with anti-HBD-2 antibody plus recombinant HBD-2 protein was higher than that in the control in 5637 (P < 0.01) and T24 cells (P < 0.05). Mycobacterium bovis BCG decreased bladder cancer cell viability, and anti-HBD-2 antibody prevented the inhibitory role of HBD-2 on the anti-proliferative effects of M. bovis BCG in bladder cancer cells CONCLUSION: Bladder cancer cells produce HBD-2 when they are infected by BCG to defend themselves against BCG internalisation, which plays an important role during the initiation and propagation of the immunotherapeutic response in bladder cancer cells.	bladder
ARF regulates the stability of p16 protein via REGγ-dependent proteasome degradation.	The cell-cycle regulatory gene INK4A-ARF (CDKN2A) has two alternative transcripts that produce entirely different proteins, namely p14(ARF) and p16, which have complementary functions as regulators of p53 and pRB tumor suppressor pathways, respectively. The unusual organization of INK4A-ARF has long led to speculation of a need for coordinated regulation of p14(ARF) and p16. We now show that p14(ARF) (ARF) regulates the stability of p16 protein in human cancer cell lines, as well as in mouse embryonic fibroblasts (MEFs). In particular, ARF promotes rapid degradation of p16 protein, which is mediated by the proteasome and, more specifically, by interaction of ARF with one of its subunits, REGγ. Furthermore, this ARF-dependent destabilization of p16 can be abrogated by knockdown of REGγ or by pharmacologic blockade of its nuclear export. Thus, our findings have uncovered a novel crosstalk of 2 key tumor suppressors mediated by a REGγ-dependent mechanism. The ability of ARF to control p16 stability may influence cell-cycle function. IMPLICATIONS: The ability of ARF to control p16 stability may influence cell cycle function. Visual Overview: http://mcr.aacrjournals.org/content/current.	bladder
Primary bladder preservation treatment for urothelial bladder cancer.	BACKGROUND: Significant advancements have occurred in surgical procedures and chemoradiation therapy for bladder preservation. METHODS: This review addresses primary treatment options for bladder cancer, including an overview of bladder-sparing strategies. RESULTS: Surgical series demonstrate that highly selected patients with cT2N0M0 urothelial bladder cancers can be managed with partial cystectomy and bilateral pelvic lymphadenectomy. For patients with cT2N0M0 to cT4aN0M0 urothelial bladder cancers, neoadjuvant chemotherapy followed by radical cystectomy or maximal transurethral resection of the bladder tumor (TURBT) followed by chemoradiation therapy results in equivalent survival rates. However, each treatment option has a different impact on quality of life. Current chemoradiation therapy trials are evaluating novel approaches to improve outcomes. CONCLUSIONS: Maximal TURBT followed by chemoradiation therapy demonstrated equivalent survival with radical cystectomy while preserving bladder function in the majority of patients. Future efforts will be directed toward improving survival and quality of life.	bladder
Air cystoscopy is superior to water cystoscopy for the diagnosis of active hematuria.	PURPOSE: We evaluated the clinical use of air cystoscopy, including its possible advantages and disadvantages over water cystoscopy. MATERIALS AND METHODS: Two independent observers prospectively studied consecutive patients who underwent water cystoscopy first and then air cystoscopy at our center from May to September 2012. The indication for rigid cystoscopy in the operating room was noted independently by either observer. Findings after rigid cystoscopy were correlated with the results of flexible water and air cystoscopy using the Pearson correlation and Student t-test. RESULTS: Included in the study were 57 patients with active hematuria, of whom 36 had bladder cancer, and 257 with a history of bladder tumor. The cause of bleeding was clearly identified on water cystoscopy in 22 patients (38%), including tumors in 17 and prostate bleeding in 5, and by air cystoscopy in 49 (86%), including tumors in 32 and prostate bleeding in 17. For diagnosing bladder tumors air cystoscopy had higher sensitivity than water cystoscopy (88% vs 47%, p=0.003) and similar specificity (97% vs 100%, p=0.93). In the 295 patients without hematuria there was no difference in the indication compared to that identified on rigid cystoscopy (43 vs 43, p=1.0). Water cystoscopy revealed more small papillary tumors than air cystoscopy but the number was not significantly different (76 vs 67, p=0.26). All such implants identified on water cystoscopy alone were less than 2 mm. No complication specifically related to air cystoscopy was noted. CONCLUSIONS: We found no statistical difference between water and air cystoscopy in patients without hematuria. Air cystoscopy had higher sensitivity and specificity for diagnosing active hematuria while adding almost no specific complications to the procedure.	bladder
Malignant bladder pheochromocytoma with SDHB genetic mutation.	A 30-year-old man presented with micturition pain and was diagnosed with a submucosal tumor in the right wall of the bladder with metastasis to the right obturator lymph node. Transurethral resection led to a diagnosis of invasive malignant pheochromocytoma. Radical cystectomy, neobladder reconstruction and bilateral iliac lymph node dissection were performed. Genetic analysis revealed succinate dehydrogenase B-associated hereditary pheochromocytoma/paraganglioma syndrome. 10 months after the operation, he had no evidence of recurrence.	bladder
SNAI1 protein expression is an independent negative prognosticator in muscle-invasive bladder cancer.	BACKGROUND: The prognosis of muscle-invasive bladder cancer is poor. Molecular prognosticators have gained increasing attention for individualized therapeutic options because they can identify patients with different prognoses. METHODS: Tissue microarrays of formalin-fixed and paraffin-embedded tumor samples from 206 bladder cancer patients treated with cystectomy and chemotherapy were studied for SNAI1 protein expression by immunohistochemistry. SNAI1 expression was evaluated using an immunoreactive score (IRS). For statistical analysis, the patients were separated into two groups: those with tumor specimens negative for SNAI1 expression (IRS = 0), and the other positive for SNAI1 expression (IRS ≥1). RESULTS: Tumor samples from 42 patients showed negative SNAI1 expression, whereas the nuclei of tumor cells from 164 patients showed detectable nuclear staining of SNAI1. A Kaplan-Meier analysis of the bladder cancer patients with negative SNAI1 expression showed significantly reduced disease-specific survival (DSS) and progression-free survival (PFS) compared to the patients with positive expression (p = 0.010 and 0.013). A multivariate Cox regression analysis (adjusted for gender, age, tumor stage, tumor grade, lymph node metastasis, chemotherapy, and histologic subtype) again showed a significant correlation between patients lacking SNAI1 expression and DSS (p = 0.005; relative risk 2.31; 95 % confidence interval 1.28-4.17) or PFS (p = 0.004; relative risk 2.20; 95 % confidence interval 1.29-3.78) compared to patients with positive SNAI1 staining. CONCLUSIONS: Loss of SNAI1 protein expression is an independent prognosticator for PFS and DSS in bladder cancer patients treated by radical cystectomy and adjuvant chemotherapy. Its prognostic value for neoadjuvant or adjuvant chemotherapy must be evaluated in further prospective randomized controlled trials.	bladder
Clinicopathological characteristics and prognosis of Chinese patients with sarcomatoid carcinoma of the bladder.	OBJECTIVES: The purpose of this study was to retrospectively analyze the clinicopathological features and prognosis of Chinese patients diagnosed with sarcomatoid carcinoma (SC) of the bladder. METHODS: 13 patients admitted to the General Hospital of People's Liberation Army (PLA) between 1999 and 2010 (study group) and 74 Chinese patients diagnosed between 1994 and 2010 and reported in one of two Chinese databases (literature group). RESULTS: The two groups were similar in all demographic and clinical characteristics except depth of tumor invasion. SC of the bladder was most common in older males and most patients had high-grade or late-stage disease at diagnosis. The 6-month, 1-year, 2-year, and 5-years survival rates were 78.9%, 42.7%, 28.0%, and 21.0%, respectively. Analysis of the association of demographic and clinical characteristics with prognosis indicated no significant effect of sex, age, lesion location, tumor diameter, tumor type, depth of invasion, type of surgery, gross hematuria, and urinary tract infection. CONCLUSIONS: Our results suggest that the pathologic tumor stage was unrelated to prognosis. Early diagnosis and surgical intervention are preferred strategies for improvement of prognosis. The association between clinical stage and survival time requires further analysis.	bladder
[Non-invasive and invasive urothelial tumours: special challenges in uropathological diagnostics].	The current 2004 WHO classification of bladder tumors categorizes non-invasive and invasive urothelial neoplasms into prognostically relevant groups according to the histopathological cell morphology and underlying genetic changes. Although many parts of the classification have not been changed dramatically, even small changes have caused uncertainty and scepticism among urologists and pathologists in recent years. The following review article is structured into various challenges for urologists and pathologists and provides an overview of rare but clinically relevant subgroups and diagnostics, interpretation of diagnoses and pathological findings with respect to consequences for the daily clinical routine (extended diagnosis, therapy and prognosis).	bladder
Malignant perivascular epithelioid cell neoplasm (PEComa) of the urinary bladder with TFE3 gene rearrangement: clinicopathologic, immunohistochemical, and molecular features.	Recently, a small subgroup of PEComas has been recognized to harbor rearrangements involving TFE3, a gene also involved in rearrangements in translocation-associated renal cell carcinomas and alveolar soft part sarcomas. The few TFE3 rearrangement-associated PEComas reported have exhibited distinctive pathologic characteristics contrasting to PEComas in general, including predominantly epithelioid nested or alveolar morphology and underexpression of muscle markers by immunohistochemistry. In this study, we report the clinicopathologic, immunohistochemical, and molecular features of a primary urinary bladder PEComa diagnosed by transurethral resection in a 55-year-old woman that clinically mimicked urothelial carcinoma. Light microscopy demonstrated mixed spindle cell and epithelioid morphology with the epithelioid component preferentially associated with blood vessels. Immunohistochemistry revealed positive staining for HMB45, tyrosinase, MiTF, cathepsin K, smooth muscle actin, and TFE3 protein. Fluorescence in situ hybridization for the TFE3 gene revealed a split signal pattern, indicating TFE3 rearrangement. X chromosome inactivation analysis demonstrated a clonal pattern despite the heterogenous appearance of the tumor. Unfortunately, despite surgical resection and sarcoma-directed therapy, the patient died of metastatic disease 12 months after diagnosis. This report adds to the known data regarding urinary bladder PEComas and PEComas with TFE3 rearrangement, indicating that both can pursue an aggressive course. Although the few reported TFE3-rearranged PEComas have predominantly lacked a spindle cell component and expression of smooth muscle actin and MiTF by immunohistochemistry, the findings in this study indicate that these features are sometimes present in TFE3-rearranged PEComas.	bladder
Radical cystectomy versus bladder-preserving therapy for muscle-invasive urothelial carcinoma: examining confounding and misclassification biasin cancer observational comparative effectiveness research.	OBJECTIVES: Radical cystectomy (RC) is the standard treatment for muscle-invasive urothelial carcinoma of the bladder. Trimodality bladder-preserving therapy (BPT) is an alternative to RC, but randomized comparisons of RC versus BPT have proven infeasible. To compare RC versus BPT, we undertook an observational cohort study using registry and administrative claims data from the Surveillance, Epidemiology and End Results-Medicare database. METHODS: We identified patients age 65 years or older diagnosed between 1995 and 2005 who received RC (n = 1426) or BPT (n = 417). We examined confounding and stage misclassification in the comparison of RC and BPT by using multivariable adjustment, propensity score-based adjustment, instrumental variable (IV) analysis, and simulations. RESULTS: Patients who received BPT were older and more likely to have comorbid disease. After propensity score adjustment, BPT was associated with an increased hazard of death from any cause (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.05-1.53) and from bladder cancer (HR 1.31; 95% CI 0.97-1.77). Using the local area cystectomy rate as an instrument, IV analysis demonstrated no differences in survival between BPT and RC (death from any cause HR 1.06; 95% CI 0.78-1.31; death from bladder cancer HR 0.94; 95% CI 0.55-1.18). Simulation studies for stage misclassification yielded results consistent with the IV analysis. CONCLUSIONS: Survival estimates in an observational cohort of patients who underwent RC versus BPT differ by analytic method. Multivariable and propensity score adjustment revealed greater mortality associated with BPT relative to RC, while IV analysis and simulation studies suggest that the two treatments are associated with similar survival outcomes.	bladder
"Commentary on ""Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience."" Yafi FA, Aprikian AG, Fradet Y, Chin JL, Izawa J, Rendon R, Estey E, Fairey A, Cagiannos I, Lacombe L, Lattouf JB, Bell D, Saad F, Drachenberg D, Kassouf W. Department of Surgery (Urology), McGill University, Quebec, Canada: BJU Int 2012;110(9):1317-23 [Epub 2012 Apr 13]."	Study Type-Prognosis (cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Radical cystectomy with pelvic lymph node dissection is recognized as the standard of care for carcinoma invading bladder muscle and for refractory non-muscle-invasive bladder cancer. Owing to high recurrence and progression rates, a two-pronged strict surveillance regimen, consisting of both functional and oncological follow-up, has been advocated. It is also well recognized that more aggressive tumours with extravesical disease and node-positive disease recur more frequently and have worse outcomes. This study adds to the scant body of literature available regarding surveillance strategies after radical cystectomy for bladder cancer. In the absence of any solid evidence supporting the role of strict surveillance regimens, this extensive examination of recurrence patterns in a large multi-institutional project lends further support to the continued use of risk-stratified follow-up and emphasizes the need for earlier strict surveillance in patients with extravesical and node-positive disease. OBJECTIVES: To review our data on recurrence patterns after radical cystectomy (RC) for bladder cancer (BC). To establish appropriate surveillance protocols. PATIENTS AND METHODS: We collected and pooled data from a database of 2287 patients who had undergone RC for BC between 1998 and 2008 in eight different Canadian academic centres. Of the 2287 patients, 1890 had complete recurrence information and form the basis of the present study. RESULTS: A total of 825 patients (43.6%) developed recurrence. According to location, 48.6% of recurrent tumours were distant, 25.2% pelvic, 14.5% retroperitoneal and 11.8% to multiple regions such as pelvic and retroperitoneal or pelvic and distant. The median (range) time to recurrence for the entire population was 10.1 (1-192) months with 90 and 97% of all recurrences within 2 and 5 years of RC, respectively. According to stage, pTxN+ tumours were more likely to recur than p ≥ T3N0 tumours and p ≤ T2N0 tumours (5-yr RFS 25% vs. 44% vs. 66% respectively, P < 0.001). Similarly, pTxN+ tumours had a shorter median time to recurrence (9 months, range 1-72 months) than p ≥ T3N0 tumours (10 months, range 1-70 months) or p ≤ T2N0 tumours (14 months, range 1-192 months, P < 0.001). CONCLUSIONS: Differences in recurrence patterns after RC suggest the need for varied follow-up protocols for each group. We propose a stage-based protocol for surveillance of patients with BC treated with RC that captures most recurrences while limiting over-investigation.	bladder
The role of methylation in urological tumours.	Alterations in DNA methylation have been described in human cancer for more than thirty years now. Since the last decade DNA methylation gets more and more important in cancer research. In this review the different alterations of DNA methylation are discussed in testicular germ cell tumours, Wilms'tumours, renal cell carcinomas, urothelial cell carcinomas of the bladder and adenocarcinomas of the prostate. Eventually, the potential use in diagnostics, prognostics and therapy are discussed.	bladder